Abstract
Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13–1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12–1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03–1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19–2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06–1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.
Highlights
Coronary artery disease (CAD), which is recognized as a major public health problem, has high mortality and morbidity worldwide [1]
We identified eligible studies through a comprehensive literature search to determine whether an association exists between X-ray repair cross complementing protein 1 (XRCC1) gene polymorphisms and CAD susceptibility
One possible mechanism for the progression of atherosclerosis is via DNA damage, which is caused by the generation of oxidative stress, the accumulation of reactive oxygen species (ROS), the metabolism of toxic byproducts, and ionizing radiation [4,5,6]
Summary
Coronary artery disease (CAD), which is recognized as a major public health problem, has high mortality and morbidity worldwide [1]. One possible mechanism for the progression of atherosclerosis is via DNA damage, which is caused by the generation of oxidative stress, the accumulation of reactive oxygen species (ROS), the metabolism of toxic byproducts, and ionizing radiation [4,5,6]. One of the most important components for the efficient repair of SSBR and BER is X-ray repair cross complementing protein 1 (XRCC1) [10,11,12]. It has a role as a scaffold coordinating other proteins in the DNA repair complex. The XRCC1 gene is located on chromosome 19q13.2–13.3, it consists of 17 exons and encodes a protein of 633 amino acids [13]
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